NITE - Chemical Management Field

GHS Classification Result （Revision of the past classification result）

Chemical Name：1,4-Dioxane
CAS：123-91-1

Result：


ID:	21B3131
Classifier:	Ministry of Health, Labour and Welfare （MHLW）, Ministry of the Environment （MOE）
Year Classified:	FY2009
Reference Manual:	GHS Classification Guidance by the Japanese Government （March, 2009）

PHYSICAL HAZARDS

Hazard class		Classification	Symbol	Signal word	Hazard statement	Precautionary statement	Rationale for the classification
1	Explosives	Not applicable	-	-	-	-	There are no chemical groups associated with explosive properties present in the molecules.
2	Flammable gases （including chemically unstable gases）	Not applicable	-	-	-	-	Liquid (GHS definition)
3	Aerosols	Not applicable	-	-	-	-	Not aerosol products
4	Oxidizing gases	Not applicable	-	-	-	-	Liquid (GHS definition)
5	Gases under pressure	Not applicable	-	-	-	-	Liquid (GHS definition)
6	Flammable liquids	Category 2		Danger	H225: Highly flammable liquid and vapour	P303+P361+P353: IF ON SKIN （or hair）: Remove/Take off immediately all contaminated clothing. Rinse skin with water/shower. P370+P378: In case of fire: Use ... for extinction. P403+P235: Store in a well-ventilated place. Keep cool. P210: Keep away from heat/sparks/open flames/hot surfaces. - No smoking. P233: Keep container tightly closed. P240: Ground/bond container and receiving equipment. P241: Use explosion-proof electrical/ventilating/lighting/.../equipment. P242: Use only non-sparking tools. P243: Take precautionary measures against static discharge. P280: Wear protective gloves/protective clothing/eye protection/face protection. P501: Dispose of contents/container to ...	Classified into Category 2 since flash point is 12 degC (ICSC (2005)) and boiling point is 101 degC. The substance is classified into Class 3, PG II in UNRTDG (UN1165).
7	Flammable solids	Not applicable	-	-	-	-	Liquid (GHS definition)
8	Self-reactive substances and mixtures	Not applicable	-	-	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9	Pyrophoric liquids	Not classified	-	-	-	-	Auto-ignition point is 180 degC (ICSC (2005)) exceeding 70 degC.
10	Pyrophoric solids	Not applicable	-	-	-	-	Liquid (GHS definition)
11	Self-heating substances and mixtures	Classification not possible	-	-	-	-	Test methods applicable to liquid substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	Not applicable	-	-	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At).
13	Oxidizing liquids	Not applicable	-	-	-	-	The substance is an organic compound containing oxygen which is chemically bonded only to carbon.
14	Oxidizing solids	Not applicable	-	-	-	-	Liquid (GHS definition)
15	Organic peroxides	Not applicable	-	-	-	-	Organic compounds containing no bivalent -O-O- structure
16	Corrosive to metals	Classification not possible	-	-	-	-	No data available.

HEALTH HAZARDS

Hazard class		Classification	Symbol	Signal word	Hazard statement	Precautionary statement	Rationale for the classification
1	Acute toxicity （Oral）	Not classified	-	-	-	-	LD50 values are 4200 mg/kg (Initial Environmental Risk Assessment of Chemicals (Ministry of Environment) vol. 2 (2003)), 5170 mg/kg (Hazard Assessment Report (CERI, NITE) (2006)), 5170 mg/kg (DFGOT vol. 20 (2005)), 5200 mg/kg (IARC 11 (1976)), 5345 mg/kg (EU-RAR No. 21 (2002)), 5400 mg/kg (ACGIH (7th, 2001)), 6300 mg/kg (DFGOT vol. 20 (2005)), 6370 mg/kg (EU-RAR No. 21 (2002)), 6500 mg/kg (EU-RAR No. 21 (2002)), 7300 mg/kg (Hazard Assessment Report (CERI, NITE) (2006)) and 7339 mg/kg (EU-RAR No. 21 (2002)) for rats. Since nly one value, 4200 mg/kg (Initial Environmental Risk Assessment of Chemicals (Ministry of Environment) vol. 2 (2003)) corresponds to Category 5 and all of the other values correspond to "Not classified" in GHS classification, the substance was classified as "Not classified".
1	Acute toxicity （Dermal）	Not classified	-	-	-	-	Based on a LD50 value of 2100 mg/kg for rats (Hazard Assessment Report (CERI, NITE) (2006)), the substance was classified as "Not classified" (correspond to Category 5 in GHS classification).
1	Acute toxicity （Inhalation: Gases）	Not applicable	-	-	-	-	Liquid (GHS definition)
1	Acute toxicity （Inhalation: Vapours）	Category 4		Warning	H332: Harmful if inhaled	P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P261: Avoid breathing dust/fume/gas/mist/vapours/spray. P271: Use only outdoors or in a well-ventilated area. P312: Call a POISON CENTER or doctor/physician if you feel unwell.	From LC50 values of 46 mg/L (2h) (Hazard Assessment Report (CERI, NITE) (2006), Initial Environmental Risk Assessment of Chemicals (Ministry of Environment) vol. 2 (2003)) and 51.3 mg/L (4h) (EU-RAR No. 21 (2004), ACGIH (7th, 2001)) in rat inhalation (vapour) exposure tests, the 4-hour equivalent LC50 values are calculated to be 9158 ppm and 14236 ppm, respectively. The saturated vapour pressure concentration at the saturated vapour pressure of 38.1 mmHg (25 degC) (5079 Pa (25 degC)) (HSDB (2005)) is 50132 ppm. Since the above LC50 values are lower than 90% of saturated vapour pressure concentration, classification criteria for ppm were adopted as vapour with almost no included mists. The substance was classified into Category 4. The alteration of classification is due to amendment of the guidance.
1	Acute toxicity （Inhalation: Dusts and mists）	Classification not possible	-	-	-	-	No data available.
2	Skin corrosion/irritation	Category 2		Warning	H315: Causes skin irritation	P302+P352: IF ON SKIN: Wash with plenty of soap and water. P332+P313: If skin irritation occurs: Get medical advice/attention. P264: Wash ... thoroughly after handling. P280: Wear protective gloves/protective clothing/eye protection/face protection. P321: Specific treatment （see ... on this label）. P362: Take off contaminated clothing and wash before reuse.	Based on results of "moderately irritating" in a rabbit skin irritation test (open Draize test) (Hazard Assessment Report (CERI, NITE) (2006)) and "slightly irritating" in a rabbit, rat and mouse skin irritation tests (EU-RAR No. 21 (2002)), the substance was classified into Category 2.
3	Serious eye damage/eye irritation	Category 2A		Warning	H319: Causes serious eye irritation	P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. P337+P313: If eye irritation persists: Get medical advice/attention. P264: Wash ... thoroughly after handling. P280: Wear protective gloves/protective clothing/eye protection/face protection.	Although obvious positive reactions are reported for exposed humans, there is no report of corrosive (Hazard Assessment Report (CERI, NITE) (2006), EU-RAR No. 21 (2002)). In a rabbit eye irritation test, "severe chemosis, slight corneal opacity and conjunctival redness (conjunctival redness persisted to day 8 in one animal)" were observed (EU-RAR No. 21 (2002)). Based on the data, the substance was classified into Category 2A. As relevant information, in EU classification, the substance is classified into R36/37.
4	Respiratory sensitization	Classification not possible	-	-	-	-	No data available.
4	Skin sensitization	Classification not possible	-	-	-	-	In a guinea pig skin sensitizing test (Directive 84/449/EEC, B.6) (GLP), a negative result is reported (EU-RAR No. 21 (2002), original literature BASF (1993)). On the other hand, positive results are reported in human patch tests (EU-RAR No. 21 (2002), NICNASPEC No. 7 (1998)). Classification was not possible.
5	Germ cell mutagenicity	Not classified	-	-	-	-	Although there are positive and negative results in micronucleus test by oral gavage to mice (ATSDR (2007), Hazard Assessment Report (CERI, NITE) (2006), NICNAS No. 7 (1998)), the substance was classified as "Not classified" based on expert's decision for reliability of the test. There are reports of positive rat hepatic cell DNA damage test, DNA synthesis test and DNA repair test (Hazard Assessment Report (CERI, NITE) (2006), NICNAS No. 7 (1998), PATTY (5th, 2001)) and negative Ames test, mouse lymphoma test and chromosomal aberration test (Hazard Assessment Report (CERI, NITE) (2006)).
6	Carcinogenicity	Category 2		Warning	H351: Suspected of causing cancer	P308+P313: IF exposed or concerned: Get medical advice/attention. P201: Obtain special instructions before use. P202: Do not handle until all safety precautions have been read and understood. P281: Use personal protective equipment as required. P405: Store locked up. P501: Dispose of contents/container to ...	Based on the classifications of "2B" in IARC (IARC (1999)) and "3" in EU classification, the substance was classified into Category 2. As relevant information, the substance is classified into "R" in NTP (NTP (2005)), "B2" in EPA and "2B" in Japan Society For Occupational Health (JSOH). In a drinking water test in rats, increased incidences of malignant tumor in the nasal cavity (mostly squamous cell carcinoma), hepatocellular carcinoma, hepatocellular adenoma and mesothelioma in the peritoneum were observed in males, and increased incidences of malignant tumor in the nasal cavity (mostly squamous cell carcinoma), hepatocellular adenoma and carcinoma were observed in the females. Based on these results, carcinogenicity was indicated (Results from Carcinogenicity tests (Ministry of Health, Labour and Welfare) (1990)).The Ministry of Health, Labour and Welfare has made a public announcement on guidelines in order to prevent the impairment of worker's health based on Industrial Safety and Health Act Article 28-3 (1992).
7	Reproductive toxicity	Classification not possible	-	-	-	-	In developmental toxicity tests in rats by oral administration (Hazard Assessment Report (CERI, NITE) (2006)) or inhalation exposure (Initial Environmental Risk Assessment of Chemicals (Ministry of the Environment) vol. 2 (2003)) during the organogenesis period, no adverse effects on fetal development were seen while decreased fetal weight and delayed ossification were observed in some tests. However, classification was not possible due to lack of data for sexual function and fertility.
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system), Category 3 (narcotic effects, respiratory tract irritation)		Danger Warning	H370: Causes damage to organs (central nervous system) H336: May cause drowsiness or dizziness (narcotic effects, respiratory tract irritation)	P307+P311: IF exposed: Call a POISON CENTER or doctor/physician. P260: Do not breathe dust/fume/gas/mist/vapours/spray. P264: Wash ... thoroughly after handling. P270: Do not eat, drink or smoke when using this product. P321: Specific treatment （see ... on this label）. P405: Store locked up. P501: Dispose of contents/container to ... P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P403+P233: Store in a well-ventilated place. Keep container tightly closed. P261: Avoid breathing dust/fume/gas/mist/vapours/spray. P271: Use only outdoors or in a well-ventilated area. P312: Call a POISON CENTER or doctor/physician if you feel unwell.	Based on findings of dizziness, sleepiness and unconsciousness in humans following inhalation exposure (Initial Environmental Risk Assessment of Chemicals (Ministry of the Environment) vol. 2 (2003)), the substance was classified into Category 1 (central nervous system). Narcotic effects are reported in rats following inhalation at 155 mg/L (EU-RAR 21 (2002)) and rabbits following oral exposure at 6600 mg/kg (ATSDR (2007)). The substance was classified into Category 3 (narcotic effects). The substance is irritating to the nose and throat in humans (EU-RAR 21 (2002), ATSDR (2007)). In an inhalation test in rats, irritation of mucous membranes of the respiratory tract was observed (EU-RAR 21 (2002)). Based on these results, the substance was classified into Category 3 (respiratory tract irritation). Since the effects on the central nervous system (toxic symptoms) were transient and mild in degree, and were considered to correspond to narcotic effects, the data was not used as the basis of classification of central nervous system. As for liver and kidney, test data was not obtained. Other data was insufficient as evidence for classification.
9	Specific target organ toxicity - Repeated exposure	Category 1 (kidney, liver, central nervous system), Category 2 (respiratory system)		Danger Warning	H372: Cause damage to organs through prolonged or repeated exposure (kidney, liver, central nervous system) H373: May cause damage to organs through prolonged or repeated exposure (respiratory system)	P260: Do not breathe dust/fume/gas/mist/vapours/spray. P264: Wash ... thoroughly after handling. P270: Do not eat, drink or smoke when using this product. P314: Get medical advice/attention if you feel unwell. P501: Dispose of contents/container to ...	In a case report of 5 workers who died following exposure to the substance, hemorrhage and necrosis in the kidney and necrosis in the liver are reported (Hazard Assessment Report (CERI, NITE) (2006)). There is a case report that a worker who had been exposed for one week in a closed, non ventilated room without respiratory equipment showed hypertonia, neurological symptoms, kidney failure, renal cortex necrosis, severe centrilobular necrosis in the liver and demyelination and partial loss of nerve fibre tissue in the brain (EU-RAR No. 21 (2002)). Based on the data, the substance was classified into Category 1 (kidney, liver, central nervous system). In a 2-year oral test in rats, degeneration of airway epithelium was observed at 16 mg/kg/day (corresponds to Category 2) (Initial Environmental Risk Assessment of Chemicals (Ministry of the Environment) vol. 2 (2003)). Based on this data, the substance was classified into Category 2 (respiratory system).
10	Aspiration hazard	Classification not possible	-	-	-	-	No data available.

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Symbol	Signal word	Hazard statement	Precautionary statement	Rationale for the classification
11	Hazardous to the aquatic environment （Acute）	Not classified	-	-	-	-	Classified into Not classified from its 96h-LC50 >100 mg/L for fish (Oryzias latipes) (Test for the Ecological Effect of Chemical Substances (Ministry of the Environment), 1995, etc), 48h-EC50 >1000 mg/L for Crustacea (Daphnia magna) (Test for the Ecological Effect of Chemical Substances (Ministry of the Environment), 1995, etc) and 72h-ErC50 >1000 mg/L for algae (Pseudokirchneriella subcapitata) (Test for the Ecological Effect of Chemical Substances (Ministry of the Environment), 1995, etc).
11	Hazardous to the aquatic environment （Long-term）	Not classified	-	-	-	-	Classified into Not classified since it is not non-water soluble (Water solubility = 1000000 mg/L (PHYSPROP Database, 2009) and its acute toxicity is low.
12	Hazardous to the ozone layer	Classification not possible	-	-	-	-	This substance is not listed in Annexes to the Montreal Protocol.

NOTE:

* Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government, and is intended to provide a reference for preparing GHS labelling and SDS for users.
* This is a provisional English translation of classification results and is subject to revision without notice.
* The responsibility for any resulting GHS labelling and SDS referenced from this site is with users.

Reference：

Reference Manual
Definitions / Abbreviations
Model Label by MHLW	MHLW Website （in Japanese Only）
Model SDS by MHLW	MHLW Website （in Japanese Only）